Adherent cell assays have typically been performed on slides, in flasks, or in petri dishes. Cells are inspected by microscopy whereby the experimentalist seeks out each cell and images each independently for fluorescence or other indicating measurables of the experiment. Alternatively, the experimentalist may look at the effects of the entire colony of cells as a whole by measuring a global quantity, such as overall fluorescence or absorbance. The methods are not conducive to high throughput analysis, or multiplexed analysis.
Tagged (“bar-coded”) microdevices have been developed for the purpose of performing multiplexed assays. Most devices are not suited to carry cells and they do not offer any added functionality other than bar coding. One system currently marketed includes a small metal device that has a bar code pattern etched on it. This enables multiple assays to be performed simultaneously. At the end of the assay, the bar coded “beads” fall to the bottom of the container and they are read by an imaging system. Another system includes beads that can be identified by their adsorption of two dyes in differing ratios, thus enabling bead identification by the use of two photodetectors. This system works in a flow-through manner, but tends not to be able to be used with cells. At least two systems are currently marketed to enhance single cell analysis. One system allows flow-through analysis of single cells by encapsulating the cell in a spherical gel matrix, then flowing the gel balls though the analysis system (e.g., a flow cytometer). Another system provides moderately sized glass plates (0.5 mm×0.35 mm) with color codes on the side to enable cells to plate and be read by imaging. It tends not to be able to be the method used in a flow-through system, nor can the current method of manufacturing enable further miniaturization.
Thus, it is desirable to provide devices and methods that facilitate performing automated, programmable, high-throughput analysis of adherent cells.